Dopamine-dependent periadolescent maturation of corticostriatal functional connectivity in mouse.
Dopamine-dependent periadolescent maturation of corticostriatal functional connectivity in mouse.
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DOI：
10.1523/jneurosci.4421-08.2009
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发表时间：
2009-02-25
期刊：
影响因子：
--
通讯作者：
Murer MG
中科院分区：
文献类型：
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作者：
Galiñanes GL;Taravini IR;Murer MG
与早期多巴胺系统功能障碍相关的皮质纹状体信息处理改变可能有助于注意缺陷多动障碍（ADHD）。患有新生儿多巴胺耗竭病变的小鼠表现出多动症，青春期后减退，并通过精神兴奋剂减少，使人想起ADHD的某些方面。为了评估早期多巴胺耗竭是否改变了皮质纹状体功能连接的成熟，我们检查了青春期前和青春期后的多巴胺耗竭损伤或不损伤的麻醉小鼠。具体而言，我们评估了（1）纹状体神经元放电和额叶皮层场电位振荡之间的同步性和（2）纹状体神经元对额叶皮层刺激的反应。在成年对照组小鼠中，纹状体神经元自发活动较少，对皮层刺激的反应较低，并且比婴儿更能在时间上调节皮层节律。来自hypersomotor小鼠的纹状体神经元需要更多的电流来响应皮层输入，并且对正在进行的振荡的锁相较少，导致响应精细皮层命令的神经元较少。到了成年期，一些电生理缺陷减弱与hypermotionation一起，但纹状体自发活动仍然大幅上升。此外，多巴胺耗尽的动物表现出正常的运动评分表现出正常的皮质纹状体同步，这表明病变允许，但不足以出现皮质纹状体的变化和活动过度。虽然安非他明正常化hypermotorotor小鼠皮质纹状体调谐，它减少了水平活动的多巴胺耗尽的动物，无论他们的运动表型，表明安非他明修改运动通过一个平行的机制，而不是修改多巴胺耗尽。总之，纹状体活动的功能成熟在婴儿期后继续，早期多巴胺耗竭延迟皮质纹状体系统核心功能能力的成熟。
Altered corticostriatal information processing associated with early dopamine systems dysfunction may contribute to attention deficit/hyperactivity disorder (ADHD). Mice with neonatal dopamine-depleting lesions exhibit hyperactivity that wanes after puberty and is reduced by psychostimulants, reminiscent of some aspects of ADHD. To assess whether the maturation of corticostriatal functional connectivity is altered by early dopamine depletion, we examined pre- and post-adolescent urethane-anesthetized mice with or without dopamine-depleting lesions. Specifically, we assessed (1) synchronization between striatal neuron discharges and oscillations in frontal cortex field potentials and (2) striatal neuron responses to frontal cortex stimulation. In adult control mice striatal neurons were less spontaneously active, less responsive to cortical stimulation and more temporally tuned to cortical rhythms than in infants. Striatal neurons from hyperlocomotor mice required more current to respond to cortical input and were less phase-locked to ongoing oscillations, resulting in fewer neurons responding to refined cortical commands. By adulthood some electrophysiological deficits waned together with hyperlocomotion, but striatal spontaneous activity remained substantially elevated. Moreover, dopamine-depleted animals showing normal locomotor scores exhibited normal corticostriatal synchronization, suggesting that the lesion allows, but is not sufficient, for the emergence of corticostriatal changes and hyperactivity. Although amphetamine normalized corticostriatal tuning in hyperlocomotor mice, it reduced horizontal activity in dopamine-depleted animals irrespective of their locomotor phenotype, suggesting that amphetamine modified locomotion through a parallel mechanism, rather than that modified by dopamine depletion. In summary, functional maturation of striatal activity continues after infancy, and early dopamine depletion delays the maturation of core functional capacities of the corticostriatal system.